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Publication : MAP kinase links the transcription factor Microphthalmia to c-Kit signalling in melanocytes.

First Author  Hemesath TJ Year  1998
Journal  Nature Volume  391
Issue  6664 Pages  298-301
PubMed ID  9440696 Mgi Jnum  J:45333
Mgi Id  MGI:1195040 Doi  10.1038/34681
Citation  Hemesath TJ, et al. (1998) MAP kinase links the transcription factor Microphthalmia to c-Kit signalling in melanocytes. Nature 391(6664):298-301
abstractText  Germline mutations at loci encoding the transcription factor Microphthalmia (Mi), the cytokine receptor c-Kit, or its ligand Steel factor (S1) result in strikingly similar defects in mast cell and melanocyte development. Here we describe a biochemical link between Kit signalling and the activity of Mi. Stimulation of melanoma cells with S1 results in activation of MAP kinase, which in turn phosphorylates Mi at a consensus target serine. This phosphorylation upregulates Mi transactivation of the tyrosinase pigmentation gene promoter. In addition to modulating pigment production, such signalling may regulate the expression of genes essential for melanocyte survival and development. The pathway represents a new application of the general MAP kinase machinery in transducing a signal between a tissue-specific receptor at the cell surface and a tissue-specific transcription factor in the nucleus.
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